PROJECT SUMMARY This is a renewal application of a training program at Icahn School of Medicine at Mount Sinai that is currently in its 17th year. In previous project periods, we have developed an innovative program in pharmacological sciences that has helped to establish Mount Sinai as one of the leaders in the nascent field of systems pharmacology. We were early advocates of introducing quantitative and computational training for all PhD candidates in biomedical sciences, and this remains the cornerstone principle of our curriculum. In coursework, students apply quantitative/computational approaches through problem solving and active learning exercises, and fundamental biological concepts underlying drug discovery and drug action are communicated within a disease context that promotes engagement. In addition to the rigorous and innovative curriculum, trainees in our program benefit from activities that enhance the research experience, including journal clubs, Works-in- Progress seminars, an annual retreat focused on career development, and an annual systems pharmacology symposium that provides networking opportunities. The coming project period will build on these successes and introduce new initiatives including flipped classrooms to maximize trainee flexibility, a new course that will be co-taught by pharmaceutical industry scientists, and formal training for all program mentors. For dissertation research, trainees can be mentored by any of 42 well-funded investigators with expertise in approaches in varied areas of pharmacology such as structure-based drug design, mathematical modeling of pathophysiology and drug action, and bioengineering. Students address cutting edge issues that must be solved to develop safe and effective therapeutics in disease areas such as cancer, cardiovascular disease, neurological disorders, diabetes, and kidney and liver disease. This structure has proven highly effective at producing successful young scientists. Trainees who have completed the program during the past 10 years have finished their PhDs in an average of 5.1 years and have typically produced nearly 5 total publications (average 4.88) and over 2 first author publications (average 2.2) resulting from their time in training at Mount Sinai. Program alumni have gone on to successful careers that collectively address many aspects of pharmacological sciences, both in academia and in the pharmaceutical industry. We aim to continue to innovate and develop trainees who will become tomorrow?s leaders in pharmacology and address the urgent need for new approaches in drug development.